Process for the purification of 1,3-diketones

ABSTRACT

A process for the purification of 1,3-diketones comprising reacting a 1,3-diketone with an earth metal or alkaline earth metal complexing agent in an organic solvent, isolating, washing and decomposing the resulting complex, and isolating the purified 1,3-diketone.

[0001] The present invention relates to a novel process for thepurification of 1,3-diketones or for isolating pure 1,3-diketones fromreaction mixtures containing such 1,3-diketones.

[0002] The process in accordance with the present invention comprises

[0003] a) reacting a 1,3-diketone with an earth metal or alkaline earthmetal complexing agent in an organic solvent to form a complex,

[0004] b) isolating said complex,

[0005] c) washing said complex with an organic solvent,

[0006] d) decomposing said complex, and

[0007] e) isolating the purified 1,3-diketone.

[0008] In a preferred aspect, the invention is concerned with thepurification or isolation of 1,3-diketones of the formulaR¹—CO—CH₂—CO—R² wherein R¹ and R² are independently an aliphatic,aromatic or heterocyclic moiety. Examples of aliphatic moietiesrepresented by R¹ and/or R² are saturated aliphatic moieties, e.g.C₁₋₂₀-alkyl groups, and unsaturated aliphatic moieties, e.g.C₂₋₂₀-alkenyl or alkinyl groups, which may be straight chain or branchedand may be unsubstituted or substituted, e.g., by halogen, hydroxy,lower alkoxy or lower alkanoyloxy.

[0009] Examples of aromatic moieties R¹ and R² are mono and bicyclicmoieties such as phenyl and naphthyl which may be unsubstituted orsubstituted. Examples of heterocyclic moieties are mono- and bicyclicheterocycles containing one or more nitrogen, sulfur and/or oxygen atomsas the hetero atoms, such as pyridyl, pyrimidyl, thienyl, furyl,thiazolyl, indolyl, quinolinyl and isoquinolinyl.

[0010] In a particularly preferred aspect, the 1,3-diketone is4-tert.butyl-4′methoxy-dibenzoylmethane or isopropyl dibenzoylmethane,also known as PARSOL® 1789 and EUSOLEX® 8020, respectively, which are awidely used UV filter in cosmetic sunscreen formulations.4-tert.butyl-4′methoxy-dibenzoylmethane is conventionally prepared byaldol condensation of a 4-tert.-butyl benzoic acid derivative with4-methoxy acetophenon and is purified by recrystallisation of the crudecondensation product from methanol. By the process of the presentinvention the diketones such as 4-tert.butyl-4′methoxy-dibenzoylmethanecan be obtained in higher purity. This is particularly important becauseminor impurities tend to impart a color to the product which is unwantedfor use in cosmetic formulations.

[0011] The organic solvent used in the purification process of thepresent invention can be any organic solvent that is capable ofsolubilizing the 1,3-diketone to be purified and which is inert towardsthe complexing agent. Typical solvents are aromatic hydrocarbons, suchas benzene and, preferably, toluene. Examples of other solvents for usein the present invention are aliphatic alcohols such as methanol andethanol, ethers, such as diethyl ether, methyl tert.butyl ether,tetrahydrofuran and dioxane, and chlorinated hydrocarbons such asmethylene chloride, chloroform and chlorobenzene.

[0012] The earth metal or alkaline earth metal complexing agent can beany derivative of these metals which are capable to form a complex with1,3-diketones. Typical examples are halogenides of boron, aluminum,calcium and magnesium, in particular boron trifluoride, aluminumtrichloride, calcium chloride and magnesium chloride, as well as boricacid. The preferred complexing agent is boron trifluoride.

[0013] The purification process can be carried out by adding thecomplexing agent to a solution of crude 1,3-diketone in an appropriateorganic solvent, or by adding the complexing agent to a reaction mixturecontaining the 1,3-diketone. Suitably, equimolar amounts of the1,3-diketone and the complexing agent, preferably a slight excess, e.g.,a 10% molar excess of the complexing agent are used. Upon reaction ofthe 1,3-diketone with the complexing agent a complex is formed as asolid precipitate which can be separated and washed with an appropriatesolvent, suitably the same solvent as the one used for dissolving thecrude product or the solvent wherein the reaction for the preparation ofthe 1,3-diketone was carried out. After washing, the solid precipitatecan be decomposed by treatment with an aqueous medium comprising a basethus yielding the 1,3-diketone in high purity. The base can be any basewhich is soluble in aqueous media, such as aqueous ammonia, alkalihydroxides, carbonates or hydrogencarbonates, e.g. NaOH, KOH, Na₂CO₃ orNaHCO₃. Preferred is aqueous ammonia. Suitably, the base is used in anequimolar amount with respect to the 1,3-diketone complex or in slightmolar excess, e.g. in 10% molar excess. The decomposition of the1,3-diketone complex is suitably carried out in a solvent such asspecified earlier, particularly in an alkanol such as methanol. Inanother embodiment of the invention the pure diketone can be obtainedfrom the complex by treatment with an acid which is soluble in aqueousmedia and which is capable of forming complexes with the complexingagent, such as oxalic acid.

[0014] The invention is illustrated in more detail by the followingExamples.

EXAMPLE 1

[0015] a) 36 g (1.2 mol) of 80% sodium amide and 300 g of dry toluenewere added to a round bottom flask, which was flushed with nitrogen. Themixture was heated to 50° C. and 150.2 g (1 mol) of acetylanisole in 309g of toluene were added within 1.5 hours. After completion of theaddition, the mixture was held at 50° C. for 15 minutes whereupon 192.3g (1 mol) of p-tert.butylbenzoic acid methyl ester (prepared accordingto U.S. Pat. No. 4,387,089) were added at this temperature within 1 hourand 50 minutes. The mixture was stirred for a further 1 hour at 50° C.and then heated at 100° C. for 1 hour, after which time the productseparated out in the form of a solid precipitate. The mixture was leftto stand for 12 hours. 300 ml of ice-water followed by a mixture of 100ml of pure hydrochloric acid and 250 ml of ice-water then added. Thephases were separated and the organic phase washed twice with water anddried over sodium sulfate.

[0016] b) To the organic phase obtained in step a) 140 ml (1.1 mol) ofboron trifluoride diethyl etherate were added dropwise. When theaddition was finished, the solution was dark brown. After 5 minutes aprecipitate was formed and the mixture became red-brown. The mixture wasthen heated to 120° C. (reflux temperature) for 1 hour. Its colorchanged again, from red-brown to pink-violet. The mixture was cooled toroom temperature, the precipitate was filtered and washed with 600 ml oftert.-butyl methyl ether. After drying at high vacuum, 240 g ofBF₃-complex of 4-tert. butyl-4′-methoxy-dibenzoylmethane was obtained asa yellow-green fluorescent solid product.

[0017] c) A 6 liter three necked reaction flask equipped with refluxcondenser, stirrer and oil bath was charged with 240 g (0.67 mol) ofBF₃-complex of 4-tert. butyl-4′-methoxy-dibenzoylmethane as obtained instep b), 3.5 liter of methanol and 50 g of aqueous ammonia (25%). Themixture was heated to 70° C. (reflux temperature) overnight understirring. A clear solution was formed. After cooling with an ice bath aprecipitate was formed which was filtered off and washed with 1 liter ofaqueous methanol (75%). After drying at high vacuum, 196 g of 4-tert.butyl-4′-methoxy-dibenzoylmethane of m.p. 85.5° C. were obtained. Purityby HPLC: 99.7%.

EXAMPLE 2

[0018] a) A part of the organic phase obtained in example 1, step a) wasconcentrated and dried at high vacuum and 5 g of a brown,semicrystalline material was obtained, which contained 70% of 4-tert.butyl-4′-methoxy-dibenzoylmethane as determined by HPLC. This materialwas dissolved in 15 ml of ethanol and heated to 60° C. In a separateflask, 0.72 g of AlCl₃ was dissolved in 15 ml of ethanol, which causedan exothermic reaction. This solution was slowly added to the first one.This combined yellow solution was treated with 2 ml of aqueous ammonia(25%) and pale yellow crystals were immediately formed. The reaction wasstirred for a further 15 min at 60° C., cooled and filtered off. Theresidue was washed with water and ethanol and dried at the high vacuum.4.3 g of pale orange crystals of the corresponding Al⁺³-complex wereobtained. MS: 954 (M⁺); 645 (100%).

[0019] b) A 250 ml three necked reaction flask equipped with refluxcondenser, stirrer and oil bath was charged with 4.1 g of theAl⁺³-complex of 4-tert.butyl-4′-methoxy-dibenzoylmethane as obtained inexample 2 step a) dissolved in 50 ml of methanol and 1 ml of aqueousammonia (25%). The mixture was heated to reflux and 0.82 g of oxalicacid dihydrate was added and the hot solution was filtered. The filtratewas cooled and 4-tert.butyl-4′-methoxy-dibenzylmethane precipitated. Theprecipitate was filtered off and dried at high vacuum to yield 2.33 g ofpure product mentioned above. The filtrate was treated with a smallamount of water and a second fraction of4-tert.butyl-4′-methoxy-dibenzoylmethane precipitated, which wasfiltered off and dried to yield another 1 g of pure product.

EXAMPLE 3

[0020] In analogy to the procedure described in example 2a) but usingMgCl₂ instead of AlCl₃ the MgCl₂ complex of 4-tert.-butyl-4′-methoxydibenzoylmethane was obtained from which pure, white4-tert.butyl-4′-methoxy dibenzoylmethane was obtained in analogy toExample 2b).

EXAMPLE 4

[0021] In analogy to the procedure described in example 2a) but usingCaCl₂ instead of AlCl₃, the CaCl₂ complex of 4-tert.-butyl-4′-methoxydibenzoylmethane was obtained from which pure, white4-tert.butyl-4′-methoxy dibenzoylmethane was obtained in analogy toExample 2b).

What is claimed is:
 1. A process for the purification of 1,3-diketoneswhich comprises a) reacting a 1,3-diketone with an earth metal oralkaline earth metal complexing agent in an organic solvent to form acomplex, b) isolating said complex, c) washing said complex with anorganic solvent, d) decomposing said complex, and e) isolating thepurified 1,3-diketone.
 2. A process according to claim 1 wherein thecomplexing agent is boron trifluoride.
 3. The process according to claim1 or 2, wherein the organic solvent used in the reaction is an aromatichydrocarbon.
 4. The process according to claim 3, wherein the aromatichydrocarbon is toluene.
 5. The process according to any one of claims 1to 4 wherein the complex is decomposed by treatment with aqueous ammoniasolution.
 6. The process according to any one of claims 1 to 5 whereinthe 1,3-diketone is a compound of the formula R¹—CO—CH₂—CO—R² wherein R¹and R² are independently an aliphatic, aromatic or heterocyclic moiety.7. The process according to claim 6, wherein R¹ and R² are independentlyphenyl or substituted phenyl.
 8. The process according to claim 7,wherein R¹ is p-tert.butylphenyl and R² is p-methoxyphenyl.
 9. A processfor preparing pure 1,3-diketones substantially as describedhereinbefore, especially with reference to the Examples.
 10. ABF₃-complex of 4-tert.butyl-4′-methoxy-dibenzoylmethane.